Treatment of Acute Postoperative Hypertension in Cardiac Surgery Patients: An Efficacy Study of Clevidipine Assessing Its Postoperative Antihypertensive Effect in Cardiac Surgery-2 (ESCAPE-2), a Randomized, Double-Blind, Placebo-Controlled Trial

Neil Singla, MD*, David C. Warltier, MD, PhD, Sweeta D. Gandhi, MD, Philip D. Lumb, MBBS, FCCM, Robert N. Sladen, MBChB, MRCP(UK), FRCP(C), FCCM, Solomon Aronson, MD, FACC, FCCP, FAHA||, Mark F. Newman, MD||, Howard L. Corwin, MD, FCCM¶# for the ESCAPE-2 Study Group
From the *Department of Anesthesia, Huntington Memorial Hospital, Pasadena, California; Department of Anesthesiology, VA Medical Center, Milwaukee, Wisconsin; Department of Anesthesiology, Keck School of Medicine of the University of Southern California, Los Angeles, California; Department of Anesthesiology, Colombia University College of Physicians and Surgeons, New York, New York; ||Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; and Departments of ¶Medicine and #Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Address correspondence and reprint requests to Neil Singla, MD, Huntington Memorial Hospital, 100 West CA Blvd, Pasadena, CA 91105. Address e-mail to neil@lotuscr.com.

Abstract

BACKGROUND: Acute postoperative hypertension is a well-known complication of cardiac surgery and is associated with postoperative morbidity. Clevidipine, an ultrashort-acting, third-generation dihydropyridine calcium channel blocker, exerts vascular-selective, arterial-specific vasodilation to decrease arterial blood pressure without negatively impacting cardiac function. In this double-blind, placebo-controlled trial, we examined the efficacy and safety of clevidipine in treating postoperative hypertension in cardiac surgery patients.

METHODS: Two hundred six patients undergoing cardiac surgery were randomized preoperatively. Of these, 110 met postrandomization inclusion criteria for the study [systolic blood pressure (SBP) 140 mm Hg within 4 h of admission to a postoperative setting, and clinically assessed as needing SBP reduction by 15% from baseline]. Patients received an infusion of either clevidipine (0.4–8.0 µg kg–1 min–1) or 20% lipid emulsion (placebo) for 30 min to a maximum of 1 h unless treatment failure occurred sooner. The primary end point was the incidence of treatment failure, defined as the inability to decrease SBP by 15% from baseline, or the discontinuation of study treatment for any reason within the 30-min period after study drug initiation.

RESULTS: Clevidipine-treated patients had a significantly lower incidence of treatment failure than placebo patients [8.2% (5 of 61) vs 79.6% (39 of 49), P < 0.0001]. Treatment success was achieved in 91.8% of clevidipine-treated patients. Median time to target SBP with clevidipine was 5.3 min (95% confidence interval, 4–7 min). No clinically significant increase in heart rate from baseline was observed. Adverse event rates were similar for both treatment groups.

CONCLUSIONS: Clevidipine is effective and safe in the rapid treatment of acute postoperative hypertension after cardiac surgery.